The adhesion of clots in wounds contributes to hemostasis and can be enhanced by coagulation factor XIII

Abstract

The adhesion of blood clots to wounds is necessary to seal injured vasculature and achieve hemostasis. However, it has not been specifically tested if adhesive failure of clots is a major contributor to rebleeding and what mechanisms prevent clot delamination. Here, we quantified the contribution of adhesive and cohesive failure to rebleeding in a rat model of femoral artery injury, and identified mechanisms that contribute to the adhesive strength of bulk clots in a lap-shear test in vitro. In the rat bleeding model, the frequency of clot failures correlated positively with blood loss (R = 0.81, p = 0.014) and negatively with survival time (R = − 0.89, p = 0.0030), with adhesive failures accounting for 51 ± 14% of rebleeds. In vitro, adhesion depended on fibrinogen and coagulation factor XIII (FXIII), and supraphysiological FXIII improved adhesive strength. Furthermore, when exogenous FXIII was topically applied into the wound pocket of rats, eleven adhesive failures occurred between eight rats, compared to seventeen adhesive failures between eight untreated rats, whereas the number of cohesive failures remained the same at sixteen in both groups. In conclusion, rebleeding from both adhesive and cohesive failure of clots decreases survival from hemorrhage in vivo. Both endogenous and exogenous FXIII improves the adhesive strength of clots.

Effects of Algan hemostatic agent foam in rat femoral artery injury model: A randomized animal trial

“…Bertram et al [25] analyzed the effect of intravenous synthetic platelet injections on rat femoral artery incision models and reported that synthetic platelets led to a reduction in bleeding nearly to half that of the control group. Studies have found no significant contribution from administration of extra amounts of physiological hemostatic substances to hemostasis when they were administered intravenously [26,27]. In studies conducted to test the effectiveness of AHA in heparinized/non-heparinized rat splenectomy and heparinized/non-heparinized rat hepatectomy models, AHA was found to lead to a decrease in the average time to achieve hemostasis by 97.7% and 98%, respectively [13,16].…”

Hemostatic biomaterials to halt non-compressible hemorrhage

“…The gap was filled recently with a rodent study, showing that both adhesive and cohesive failures of blood clots lead to rebleeding and decrease survival from hemorrhage in vivo . 21 Substantiating the direct link between clot mechanics and hemostasis requires further investigation.…”

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing

“…Preclinical studies in models of THS and experimental burn have suggested that FXIII supplementation may ameliorate THS-induced organ failure [38,39]. Furthermore, in preclinical studies using an experimental haemorrhagic shock model high doses of FXIII promoted effective haemostasis for trauma-associated coagulopathy in vitro and in vivo [40,41]. FXIII also improved clot adhesion in wounds in a standardised bleeding model [41].…”

“…Furthermore, in preclinical studies using an experimental haemorrhagic shock model high doses of FXIII promoted effective haemostasis for trauma-associated coagulopathy in vitro and in vivo [40,41]. FXIII also improved clot adhesion in wounds in a standardised bleeding model [41]. In vitro, FXIII improved clot strength and increased resistance to hyperfibrinolysis (measured by rotational thromboelastometry [ROTEM]) and significantly decreased bleeding and prolonged survival in vivo [42].…”